Oligodendrocytes are the myelinating glial cells of the central nervous system (CNS). The appearance of these myelinating cells during evolution is thought to have enabled the vertebrate nervous system to grow large and complex by allowing saltatory conduction of nervous impulses. These cells arise at discrete places and at discrete times from the ventricular zone of the developing neural tube. The molecular mechanisms that control the initial decision of multipotent CNS neural stem cells to become oligodendrocytes are not fully understood. Some growth factors have been identified that seem to bias stem cells towards an oligodendrocyte (ODC) fate.
Oligodendrocytes and their precursors (oligodendrocyte precursors or OLPs) are highly relevant to human disease. Deficiencies in the number, function or survival of these cells can cause devastating demyelinating diseases. A variety of demyelinating diseases exist in humans, wherein the myelin sheaths are lost, usually through the death of mature oligodendrocytes. One principal example, multiple sclerosis (MS). On the other hand, oncogenic transformation and overproduction of cells in this lineage, conversely, leads to brain tumors such as oligodendrogliomas and glioblastoma multiforme.
Multiple Sclerosis (MS) is an inflammatory disease of the Central Nervous System (CNS). Multiple Sclerosis affects roughly two and a half million people worldwide and is one of the most common causes of neurological disability in young adults. Typically, patients with MS present with a relapsing/remitting form of the disease, characterized by acute demyelinating episodes followed by the generation of new oligodendrocytes, remyelination, and functional recovery. However, remyelination is an inconsistent event in this disease, and the accumulated load of lesions that fail to remyelinate results in progressive neurological deterioration, in part because the capacity to generate new oligodendrocytes becomes limited.
Predominantly, it is a disease of the “white matter” tissue, which comprises nerve fibres responsible for transmitting communication signals both internally within the CNS and between the CNS and the nerves supplying rest of the body. In MS patients, patches of damage or “plaques or lesions” appear in seemingly random areas of the CNS white matter. At the site of a lesion, a nerve insulating material—myelin—is lost. Clinically, MS is a hard condition to characterize because it is very unpredictable and variable. Depending on which areas of the CNS are affected and how badly they are damaged, the type and severity of symptoms can vary greatly. No two people get MS in exactly the same way, and the expression of each individual's disease is as unique as their fingerprints. However, the different courses of the disease, both within an individual and within the whole population, principally differ in their timing, location and severity. Underneath similar processes (including demyelination and sometimes other forms of nerve degeneration) are going on.
Although recent research indicates that the biochemical make-up of lesions may vary between different forms of the disease, this is not the reason why people with MS (PwMS) have such widely differing symptoms—it's because nerve damage to one site usually causes completely different symptoms than damage to another. In general, MS patients can experience partial or complete loss of any function that is controlled by, or passes through, the brain or spinal cord.
There is still no cure for MS, although there are various strategies available to modify the disease course, treat exacerbations, manage symptoms, and improve function and safety. In combination, these treatments enhance the quality of life for people living with MS.
Oligodendrogliomas comprise a class of glial tumors in which the oligodendroglial cell is the cell predominant cell type. Normally, oligodendroglial cells form myelin—the fatty substance which surrounds the axons of nerve cells and provides the insulation which makes nerve cell electrical transmission faster and more efficient. Oligodendrogliomas probably evolve from a mixed glioma which has in turn evolved from primitive precursor or stem cells. The mixed glioma which contains astrocytic and neuronal elements as wells as oligodendroglial cells and is a slow growing tumor. But each of the cell types has a certain percentage of cells capable of mitosis. In the oligodendroglioma the mitotic rate of the oligodendroglial cells has exceeded the mitotic rate of the other cells and eventually the oligodendroglial cells become the most numerous—the predominant cell type and, therefore, an oligodendroglioma.
The speed of this transformation varies widely from patient to patient and there is no consistent way of predicting the behavior of any oligodendroglioma—especially in adult patients. In general, all glial tumors, including oligodendrogliomas, will become malignant, as a matter of time and random evolution in the ability of cells within that tumor to increase their rate of mitosis. The length of time could be 30 years, or it could be 6 months.
Glioblastoma multiforme refers to a malignant neoplasm with abundant glial pleomorphism, numerous mitotic figures and giant cells, vascular hyperplasia, and focal areas of necrosis. Occurring most commonly in the fifth through seventh decades, glioblastoma multiforme usually develops in the cerebral hemispheres (more often in the frontal lobes than the temporal lobes or basal ganglia) but almost never in the cerebellum. It grows as an irregular mass in the white matter and infiltrates the surrounding parenchyma by coursing along white matter tracts, frequently involving the corpus callosum and crossing the midline to produce the characteristic “butterfly” appearance.
Forty to fifty percent of primary central nervous system tumors are gliomas. Approximately 50% of these are glioblastoma multiforme, and 7% are astrocytomas. Oligodendrogliomas and glioblastoma multiforme are some of the most aggressive and intractable forms of cancer known. The prognosis is very poor. Mean survival length after diagnosis is eight to ten months, with less than 10% survival after two years. Unfortunately, the treatments for either of these classes of diseases, at present, are inadequate and unsatisfactory.
Therefore, there is a need to provide additional treatment methods and reagents for diseases related to oligodendrocytes, including demyelination diseases such as MS, and hyperproliferation diseases such as oligodendrogliomas and glioblastoma multiforme.